Know Your Naloxone: Save a Life
Medically reviewed on Feb 10, 2017 by L. Anderson, PharmD.
The Overdose Issue
Opioids are a class of drugs that include narcotic analgesic prescription medications such as oxycodone, hydrocodone, morphine, and fentanyl, as well as the illegal drug heroin. In the US, the death rate from prescription opioid overdoses has increased 4-fold since 1999, while deaths from heroin deaths have more than quadrupled since 2010. Alarmingly, heroin and prescription pain medications resulted in the death of over 46,000 people in 2015.1
In response, several state and federal initiatives are underway to combat this epidemic. The FDA has also approved new naloxone agents that can reverse the depressed, often fatal slowed breathing that can occur with a narcotic overdose. These agents can be easily administered by families or friends to anyone experiencing an overdose. But until recently, these agents weren't easily accessible by the public.
How Do I Recognize an Opioid Overdose?
All opioids (narcotics) will produce various levels of central nervous system (CNS) depression and side effects such as drowsiness, sedation, and slowed breathing. In an overdose, you might notice stupor, coma, slurred speech, clammy skin, pinpoint pupils, and low blood pressure.
The most dangerous and often fatal side effect of an opioid overdose is respiratory depression - slowed or arrested breathing. This risk is multiplied when the narcotic is combined with alcohol or other CNS depressants. If you believe someone has overdosed on narcotics, call 911 immediately. A reversal agent called naloxone can be life-saving for patients who overdose on narcotics, although in patients dependent upon opioids, it can also cause a severe withdrawal.
What is Naloxone?
Naloxone is a medication that rapidly reverses the effects of an opioid (narcotic) overdose and is the standard treatment. It is not addictive or considered an opioid itself. Naloxone has been available in injection form to reverse the effects of opioid overdose for more than 40 years. Prior naloxone treatments required administration via a syringe and needle and were most commonly used by trained medical personnel.
Today, newer naloxone approvals come as nasal sprays and auto-injectors to make these life-saving drugs more user-friendly. In fact, most states have now passed legislation designed to improve lay-person naloxone access.
How Can Naloxone Save a Life?
Pharmacologically, naloxone is considered an opioid antagonist, meaning it blocks opioid receptors. Unlike opioids, naloxone (brand names include Narcan, Narcan Nasal, Evzio) is not a controlled substance and has no potential for abuse. In fact, naloxone has no pharmacologic action in the absence of an actual opioid overdose. It is regularly used by first responders and can be administered by lay-people with little or no training.
Naloxone can counter overdose effects, including depressed breathing, drowsiness, and loss of consciousness - usually within 2 to 3 minutes - and can be given by family members or caregivers until emergency help arrives. In families or friends that elect to carry the devices or store these medications in their home, learning how to use them ahead of time may save time.
What Are Opioids?
Naloxone reverses the effects of prescription opioid overdoses, as well as heroin, but has no action in other types of overdoses such as benzodiazepines like alprazolam (Xanax) or lorazepam (Ativan), sedatives like barbiturates, or alcohol. You should always call for emergency help when you use naloxone; you may not known what the person has overdosed on or it may be a mixture of substances. Examples of prescription opioids that may be involved in an overdose include:
- Buprenorphine (Buprenex)
- Buprenorphine transdermal system (Butrans Skin Patch)
- Codeine sulfate (Tylenol with Codeine #3, Tylenol with Codeine #4, Capital and Codeine Suspension)
- Fentanyl (Abstral, Actiq, Duragesic, Fentora, Ionsys, Onsolis)
- Hydrocodone (Hysingla ER; Zohydro ER; both abuse-deterrent formulations; Vicoprofen, Lorcet, Lortab, Norco, Vantrela ER, Vicodin)
- Hydromorphone (Dilaudid; Dilaudid HP; Exalgo)
- Meperidine (Demerol)
- Methadone (Dolophine, Methadose)
- Morphine (Kadian, MS Contin, MorphoBond, Arymo ER)
- Oxycodone (Percocet, Percodan, Roxicet, Oxaydo, OxyContin, Roxicodone)
- Oxymorphone (Opana, Opana ER)
- Pentazocine (Talwin)
- Tapentadol (Nucynta, Nucynta ER)
- Tramadol (Conzip, Rybix ODT, Ryzolt, Ultram, Ultram ER, generics)
Narcan: The Original
The first FDA-approved naloxone was injectable Narcan which became available in the early 1970's. The intravenous formulation is used in clinic and hospital settings, but an intramuscular formulation is available also, often sold in a kit with 2 syringes and 2 vials of 0.4 mg/mL naloxone and provided to emergency first-responders. The naloxone vials are also sold in a kit with nasal atomizers for use as a nasal spray. All kits contain an instruction chart for use and assembly direction.
The FDA-approved Evzio Autoinjector and Narcan Nasal Spray are now available at pharmacies but at higher costs. Narcan Nasal Spray has been approved in 2 mg and 4 mg strengths. Patients who cannot afford these medications, but need them, should call the US manufacturers (Kaleo for Evzio) or (Adapt Pharma for Narcan Nasal) to determine if they qualify for assistance.
Evzio (naloxone hydrochloride) Autoinjector
In April 2014 the FDA approved Evzio (naloxone hydrochloride) as an emergency treatment for known or suspected opioid overdose. Evzio delivers a single naloxone 0.4 mg dose via a hand-held auto-injector that can be carried in a pocket or stored in a medicine cabinet in a caregiver's home. Another plus in an emergency situation -- when Evzio is turned on, it provides verbal instructions to the user. This is an obvious advantage in a stressful, emergency situation that a lay-person might encounter.
Because naloxone may not work as long as the opioid, a second repeat dose may be needed after 2 to 3 minutes until emergency help arrives.
How to Use Evzio Autoinjector
Read the "Instructions for Use" that comes with Evzio when you get it from the pharmacy or clinic. Evzio has built-in voice instructions to help guide administration, and directions are on the label, too. When you need to use Evzio for an overdose:
- Pull Evzio from the outer case.
- Pull off the RED safety guard.
- Place the BLACK end of Evzio against the outer thigh. May administer through clothing if necessary.
- Press firmly and hold in place for 5 seconds.
- After using Evzio, get emergency medical help (call 911) right away. If symptoms return, another injection may be needed.
- The Evzio Autoinjector cannot be reused; to re-administer another dose a new Evzio case must be activated.
Narcan Nasal Spray
In November 2015 Narcan Nasal Spray 4 mg became available as the first FDA-approved nasal spray version of naloxone. A 2-mg strength was approved in Jan 2017. Narcan Nasal offers an advantage to the lay-person as, like Evzio, it is user-friendly and is easily carried in a purse or pocket or stored in the home.
In clinical studies, one dose of Narcan Nasal 4 mg resulted in similar levels to IM injected naloxone 0.4 mg/mL and at roughly the same time.
How to Use Narcan Nasal Spray
Narcan Nasal Spray can be used for adults or children. The drug is sprayed into one nostril while the person is lying on their back. Fully review directions enclosed in the box. To use:
- Remove the Narcan Nasal Spray from box. DO NOT prime the device before administering. Place your thumb on the plunger bottom and your first and middle fingers on either side of nozzle.
- Tilt the person’s head back and provide neck support with your hand.
- Gently insert the nozzle tip in one nostril until your fingers on either side of the nozzle are against the bottom of the person’s nose. Press the plunger firmly to give the full dose.
- Get emergency medical help right away after giving the first dose of Narcan Nasal Spray. Rescue breathing or CPR may be given while waiting for emergency medical help.
- If symptoms return, give another dose in the other nostril after 2 to 3 minutes using a new Narcan Nasal Spray in alternate nostrils with each dose until emergency medical assistance arrives..
Naloxone Side Effects
Common naloxone side effects may include symptoms of opioid withdrawal such as: anxiety or agitation, sweating, nausea or vomiting, runny nose, high blood pressure, and shivering. Acute withdrawal from chronic opioid use may also result in seizures, pain, and elevated heart rate.
While naloxone will reverse some, but not all, symptoms caused by a tramadol (Ultram, ConZip) overdose, the risk of seizures is also increased with naloxone administration with tramadol, and may require treatment with an anti-seizure medication.
Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine (Buprenex) and pentazocine (Talwin) may be incomplete. Larger or repeat naloxone doses may be required.
Opioid Withdrawal Symptoms
In patients who are opioid-dependent, withdrawal symptoms can occur after administration of naloxone.
Sudden opioid withdrawal symptoms can happen abruptly after receiving naloxone and may include:
- Body aches, diarrhea, increased heart rate
- fever, runny nose, sneezing
- Goose bumps
- Sweating, yawning, nausea or vomiting
- Nervousness, restlessness or irritability
- Shivering, trembling
- Stomach cramping, weakness, increased blood pressure
Good Samaritan Laws
It isn't surprising that many people involved in prescription and illegal drug misuse and overdose situations are hesitant to call for emergency help due to legal concerns. However, many states have implemented "Good Samaritan" laws which allow first responders of any kind, including family and friends, to administer naloxone without prior approval from a doctor. Most states have passed legislation to improve layperson access to naloxone. The laws vary by state, particularly with regard to immunity from prosecution if found with possession of controlled substances.
Nonetheless, naloxone works: as reported by the Morbidity and Mortality Weekly Report (MMWR) in 2015, from 1996 to June 2014 over 150,000 laypeople received naloxone training and reversed more than 26,000 overdoses.
Probuphine Implant: A New Option for Opioid Dependence
While Narcan can save a life from an overdose, a multi-pronged treatment plan is needed to rescue patients from chronic misuse of opioids. As an added weapon in the treatment of opiate addiction, the FDA approved Probuphine in May 2016 as the first buprenorphine implant for the maintenance treatment of opioid dependence.
Probuphine consists of four, one-inch-long rods that are implanted under the skin and provide a constant, low-level dose of buprenorphine for six months. In studies, 63 percent of Probuphine-treated patients had no evidence of illicit opioid use throughout the six months of treatment – similar to the 64 percent of those who responded to sublingual (under the tongue) buprenorphine alone.
The Path Forward in Saving Lives
Prescription drug addiction to opioids is a domestic threat unlike any other in the US. Concerted efforts from family, friends, health care providers, first-responders, and patients themselves are needed to combat this epidemic. New, more user-friendly antidotes to reverse an opiate overdose are available, but accessibility for all parties is needed. In time, added state legislation will most likely allow easier access to the public.
Individual medical advice should always come from your physician and pharmacist, but to keep up-to-date with the latest news, or to voice questions or concerns, consider joining the Opiate Dependence Support Group on Drugs.com.
Finished: Know Your Naloxone: Save a Life
- Wheeler E, Jones TS, Gibert M, et al. Opioid Overdose Prevention Programs Providing Naloxone to Laypersons — United States, 2014. Morbidity and Mortality Weekly Report (MMWR). CDC. June 19, 2015 / 64(23);631-635. Accessed Feb 10, 2017 at https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a2.htm
- The Network for Public Health Law. Legal Interventions to Reduce Overdose Mortality: Naloxone Access and Overdose Good Samaritan Laws. Accessed Feb 2, 2017 at https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf
- Centers for Disease Control and Prevention (CDC). Injury Prevention & Control: Opioid Overdose. Data Overview. Accessed Feb 10, 2017 at https://www.cdc.gov/drugoverdose/data/index.html
- Evzio Instructions for Use. Drugs.com. Accessed Feb 3, 2017 at https://www.drugs.com/pro/evzio.html#ABIFU
- Evzio Prescribing Information. Accessed Feb 3, 2017 at http://www.evzio.com/pdfs/Evzio PI.PDF
- Blank C. First nasal spray helps with drug overdoses. Formulary Watch. November 20, 2015. Accessed Feb 9, 2017 at http://formularyjournal.modernmedicine.com/formulary-journal/news/first-nasal-spray-helps-drug-overdoses
- Narcan Nasal Spray. Manufacturers website. Accessed Feb 10, 2017 at http://www.narcannasalspray.com/how-to-get-nns/consumer-access/
- Narcan Nasal Spray Prescribing Information. Accessed Feb 10, 2017 at http://www.narcannasalspray.com/pdf/NARCAN-Prescribing-Information.pdf